The skeleton is the third most common site of metastatic cancer, and nearly half of all cancers metastasize to bone. As a result of new and aggressive treatments, cancer patients are living longer, but at sites of skeletal metastasis, fractures occur in up to 35% of affected bones after minimal trauma, significantly impacting patient function and quality of life. Preventing fractures due to skeletal metastases depends on objective criteria that reflect the interaction of the tumor with the host bone. While much has been learned about the mechanisms of skeletal metastasis, clinicians continue to make subjective assessments regarding a patient's fracture risk and response to treatment based on plain radiographs and clinical symptoms now recognized to be inaccurate. Metastatic cancer alters both the material and geometric properties of the bone; failure to account for changes in both of these parameters limits the accuracy of current fracture prediction methodologies/scores. As it is the weakest segment through the bone that dictates the load capacity of the entire structure, we have developed a software package, called Computed Tomography-based Rigidity Analysis (CTRA), to calculate the minimal rigidity of a bone containing a neoplastic lesion. This method uses computed tomography (CT) images of the affected bone to calculate its structural rigidity, as a mechanical assay representing changes in bone tissue material and geometry induced by the neoplastic process. The accuracy of this approach for estimating load capacity and predicating pathologic fractures has been validated in ex-vivo, pre- clinical, and in-vivo studies, including a recent paper published in Clinical Cancer Research. This study was funded by the Musculoskeletal Tumor Society, which supports the commercialization of the software (please see letter of support).The software is currently being using at Boston Children's Hospital to assess fracture risk in children with benign lesions. Over the past 2 years, over 50 cases have been analyzed using CTRA at CHB, and the analysis results have been submitted to and reimbursed by insurance companies. Moreover, the commercialized product can be used in other areas such as fragility fracture prediction, metabolic and developmental musculoskeletal diseases and fracture non-unions. For this Direct Phase II SBIR submission, we propose to commercialize the software platform to make CTRA analysis available to clinicians. This work involves the establishment of a normative database of appendicular skeleton as a reference to interpret patient data; and to further refine our existing fracture threshold values for axial, bending and torsional rigidity indices to provide additional sensitivity for our analysis method. Therefore, the aims of the study are to: Develop a normative structural rigidity database for the appendicular skeleton as a reference for interpreting patient specific data; Optimize the threshold for reduction in rigidity indices that will determine fracturs from non-fractures with maximal sensitivity and specificity; and Develop the CTRA software to streamline and optimize the CTRA analysis procedure.